Nuclear magnetic resonance (NMR) spectroscopy offers tremendous opportunities for high-resolution, minimally-invasive, molecular imaging of deep tissue for the early diagnosis and treatment of disease. However, low sensitivity and complex background signals compromise biomarker detection. Recently, laser-polarized 129Xe has gained attention as an MR probe, due to its large signal (10-70% alignment of Xe nuclear spins, compared to thermal polarization of 0.00027% at 37° C. and 3 T) and wide NMR chemical-shift window (>200 ppm in water). Xenon gas is soluble in biological fluids (˜3.5 mM/atm at 37° C.), non-toxic, and readily delivered by inhalation or perfusion. Furthermore, the environmental sensitivity of xenon chemical shift and relaxation parameters should allow the detection of multiple species in solution simultaneously. Xenon represents, therefore, a useful probe for studying biological samples.
Xenon has been shown to bind cryptophane-A reversibly and with high affinity (KA=3900 M−1 at 278 K in C2D2Cl4, KA is higher in water). 129Xe that is free in aqueous solution or bound inside the cage is distinguished by a greater than 120 ppm difference in 129Xe NMR chemical shift. In order to couple 129Xe chemical shifts with specific biological processes, known methods were exploited for functionalizing the organic cage. Attaching biotin to cryptophane-A created a variety of biosensors for streptavidin, whose binding produced as much as a 4 ppm change in 129Xe chemical shift. 129Xe biosensors offer the possibility to functionalize various xenon-binding cages with different recognition units.